PROJECT SUMMARY: Exposure to carcinogens at the WTC site in combination with significant rates (~40%) of current or former smoking has raised concerns about the risk of lung cancer among WTC responders. Moreover, lung cancer is the most common cause of cancer deaths in WTC responders. The National Lung Screening Trial (NLST) demonstrated that low-dose computed tomography (LDCT) screening leads to a 20% decrease in lung cancer mortality among smokers in the general population. As a result, LDCT screening has been recommended by the United States Preventive Services Task Force (USPSTF) and is currently being implemented in WTC responders. However, extrapolating NLST results to the WTC responder population is challenging. Several factors may influence the harms and benefits of screening in this population including a unique set of lung cancer risk factors, an increased rate of false positive LDCTs due to exposure-related lung disease, high prevalence of decreased lung function (a factor that may impact treatment of screen-detected cancers), lower overall mortality due to a `healthy worker' effect, and decreased quality of life due to WTC- related physical and mental health conditions. Thus, the harms, benefits, and cost-effectiveness (CE) of lung cancer screening in the general population are likely different in WTC responders. Randomized controlled trials specific to WTC responders are unlikely. Thus, the goal of this project is to use simulation modeling to evaluate the effectiveness of LDCT screening in this unique group. The Specific Aims of the study are to: 1) enhance a well-validated lung cancer microsimulation model (the LCPM) to replicate the natural history, treatment and outcomes of lung cancer screening and estimate the benefits of LDCT screening based on current guidelines in WTC responders; 2) identify the optimal lung cancer screening regimen (i.e., duration, frequency of scans) and eligibility criteria (i.e., age, smoking history, occupational risk, WTC exposure) for smokers who were WTC responders; 3) Evaluate different follow-up evaluation protocols for positive lung cancer screening tests in WTC responders to maximize benefits and minimize harms; and 4) evaluate the CE of LDCT screening in WTC responders. To accomplish these Aims, we will enhance the well-validated Lung Cancer Policy Model (LCPM) to capture the unique harms and benefits and CE of LDCT screening in WTC responders. We will analyze several large, relevant datasets (the WTC Health Program, the WTC Chest Imaging Archive, NLST, etc.) to create new LCPM modules and modify key input parameters to accurately represent lung cancer screening in WTC responders. We will also assess the costs associated with screening to incorporate into the model and perform a CE analysis of LDCT screening. The study is innovative in evaluating the potential benefits and CE of LDCT screening in WTC responders. It will have a significant impact by defining the best screening regimen and facilitating the adoption of screening in >2,000 WTC responders that are estimated to be eligible for LDCT screening based on their smoking history.